Dihydrofolate reductase will be purified from a mutant of S. faecium and from beef liver in sufficient quantity for structural studies. The reductase from S. faecium will be compared with the isoenzyme already studied and sequence studies will be carried out on both the S. faecium and beef liver enzymes. Conditions for crystallization of the reductases or their methotrexate complexes will be studied. The preparation of Cl3-amino acids from Cl3 protein hydrolysates will be investigated for future use in structural studies employing NMR.